Advances in Photoenzyme-Catalyzed Asymmetric Radical Addition Reactions

doi:10.6023/cjoc202408004

Abstract

Photocatalysis can generate highly reactive radical species under mild reaction conditions, thereby participating in various chemical reactions. However, the precise control of chemical selectivity and enantioselectivity always remains a formidable challenge due to the high reactivity of radicals. Enzymatic catalysis, known for its green and highly selective properties, when combined with photocatalysis to form photoenzymatic catalysis, has been proven effective in controlling the selectivity of radical reactions. Consequently, this area has garnered widespread attention and rapid development. This review summarizes the recent applications of photoenzymatic catalysis in asymmetric radical addition reactions, dividing them into intramolecular and intermolecular radical additions based on the reaction type. Each type of reaction is further discussed in detail according to the generation pathway of radicals, categorized into single-electron reduction pathways and single-electron oxidation pathways. It is hoped that this review will provide valuable references for researchers and promote further development in this field.

Key words: photocatalysis, enzyme catalysis, radical addition, asymmetric catalysis

Cite this article

Chenyang Jiang, Yanli Yin, Zhiyong Jiang. Advances in Photoenzyme-Catalyzed Asymmetric Radical Addition Reactions[J]. Chinese Journal of Organic Chemistry, 2025, 45(5): 1614-1633.

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Fig. & Tab. 28

Scheme 1. Photoexcitation of flavoenzymes promotes a stereoselective radical cyclization

Scheme 2. Flavin-dependent ‘ene’-reductases facilitate asymmetric redox-neutral radical cyclization

Scheme 3. Photoenzymatic formation of reactive alkyl radicals: an asymmetric reductive cyclization

Scheme 4. Synthesis of α‑tertiary amines through photoenzymatic processes using engineered flavin-dependent “ene”-reductases

Scheme 5. Photoenzyme catalyzed dehalogenated radical intramolecular cycloaddition reaction

Scheme 6. Photoenzymatic enantioselective synthesis of oxygen-containing benzo-fused heterocycles

Scheme 7. Utilizing enzymes to regulate nitrogen-centered radicals for enantioselective hydroamination

Scheme 8. Stereodivergent photobiocatalytic radical cyclization using fatty acid photodecarboxylases

Scheme 9. Enantioselective intermolecular radical hydroalkylation catalyzed by photoenzymes

Scheme 10. Intermolecular hydroalkylation of alkenes enabled by a quaternary charge-transfer complex

Scheme 11. Enantioselective radical conjugate addition enabled by photoinduced enzymatic catalysis

Scheme 12. Ene-reductase-catalyzed enantioselective electrophilic C(sp3)—C(sp3) cross-coupling reaction

Scheme 13. Enzyme-promoted photoredox catalysis of asymmetric C—H alkylation of nitroalkanes

Scheme 14. Remote stereocontrol with azaarenes via enzymatic hydrogen atom transfer

Scheme 15. Asymmetric hydroalkylation of diazo compounds and alkenes via photoenzymatic radical catalysis

Scheme 16. Photoenzymatic asymmetric hydrosulfonylation of alkenes

Scheme 17. Photoenzymatic asymmetric carbohydroxylation of alkenes

Scheme 18. Photoenzymatic nitrogen-centered radical-mediated intermolecular asymmetric hydroamination reaction

Scheme 19. Stereoselective synthesis of amino acids through combined photoredox and pyridoxal radical biocatalysis

Scheme 20. Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling

Scheme 21. Synergistic photoenzymatic catalysis enables synthesis of α-tertiary amino acids using threonine aldolases

Scheme 22. Threonine aldolase catalyzed enantioselective α‑ alkylation of amino acids via unconventional photoinduced radical initiation

Scheme 23. Asymmetric synthesis of α‑chloroamides via photoenzymatic hydroalkylation of olefins

Scheme 24. Modular access to chiral amines via imine reductase-based photoenzymatic catalysis

Scheme 25. Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins

Scheme 26. Direct visible-light-excited flavoproteins for redox-neutral asymmetric radical hydroarylation

Scheme 27. Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis

Scheme 28. Asymmetric hydrosulfonylation of aryl sulfonates and α-methylstyrene catalyzed by photoenzymes

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